Dendrite-to-soma input/output function of continuous time-varying signals in hippocampal CA1 pyramidal neurons

We examined how hippocamal CA1 neurons process complex time-varying inputs that dendrites are likely to receive in vivo. We propose a functional model of the dendrite-to-soma input/output relationship that combines temporal integration and static-gain control mechanisms. Using simultaneous dual whole cell recordings, we injected 50 s of subthreshold and suprathreshold zero-mean white-noise current into the primary dendritic trunk along the proximal 2/3 of stratum radiatum and measured the membrane potential at the soma. Applying a nonlinear system-identification analysis, we found that a cascade of a linear filter followed by an adapting static-gain term fully accounted for the nonspiking input/output relationship between the dendrite and soma. The estimated filters contained a prominent band-pass region in the 1- to 10-Hz frequency range that remained constant as a function of stimulus variance. The gain of the dendrite-to-soma input/output relationship, in contrast, varied as a function of stimulus variance. When the contribution of the voltage-dependent current I(h) was eliminated, the estimated filters lost their band-pass properties and the gain regulation was substantially altered. Our findings suggest that the dendrite-to-soma input/output relationship for proximal apical inputs to CA1 pyramidal neurons is well described as a band-pass filter in the theta frequency range followed by a gain-control nonlinearity that dynamically adapts to the statistics of the input signal.     

Two-photon calcium imaging of network activity in XFP-expressing neurons in the mouse

Fluorescent protein (XFP) expression in postnatal neurons allows the anatomical and physiological investigation of identified subpopulations of interneurons with established techniques. However, the spatiotemporal pattern of activity of these XFP neurons within a network and their role in the functional output of the network are more challenging issues to investigate. Here we apply two-photon excitation laser scanning microscopy to mouse spinal cord locomotor networks and present the methodology by which calcium activity can be recorded in XFP-expressing neurons. Such activity can be studied both in relation to neighboring non-XFP neurons in a spinal cord slice preparation and in relation to functional locomotor output monitored by ventral root activity in the intact in vitro spinal cord. Thus the network properties and functional correlates with locomotion of identified populations of interneurons can be studied simultaneously.     

Electrophysiological diversity of layer 5 pyramidal cells in the prefrontal cortex of the rhesus monkey: in vitro slice studies

Whole cell patch-clamp recordings were employed to characterize the electrophysiological properties of layer 5 pyramidal cells in slices of the prefrontal cortex (Area 46) of the rhesus monkey. Four electrophysiologically distinct cell types were discriminated based on distinctive repetitive action potential (AP) firing patterns and single AP characteristics: regular-spiking slowly adapting type-1 cells (RS1; 62%), regular-spiking slowly adapting type-2 cells (RS2; 18%), regular-spiking fast-adapting cells (FA; 15%), and intrinsically bursting cells (IB; 5%). These cells did not differ with regard to their location in layer 5 nor in their dendritic morphology. In RS1 cells, AP threshold and amplitude did not change significantly during a 2-s spike train, whereas in RS2 and FA cells, AP threshold increased significantly and AP amplitude decreased significantly during the train. In FA cells, complete adaptation of AP firing was observed within 600 ms. IB cells displayed an all-or-none burst of three to six APs, followed by RS1-type firing behavior. RS1 cells could be further subdivided into three subtypes. Low-threshold spiking (LTS) RS1 cells exhibited an initial doublet riding on a depolarizing potential at the onset of a spike train and a prominent depolarizing afterpotential (DAP); intermediate RS1 cells (IM) exhibited a DAP, but no initial doublet, and non-LTS RS1 cells exhibited neither a DAP nor an initial doublet. RS2 and FA cells did not exhibit a DAP or initial doublets. The distinctive firing patterns of these diverse layer 5 pyramidal cells may reflect different roles played by these cells in the mediation of subcortical neuronal activity by the dorsolateral PFC.     

Differences of self-reported osteoarthritis disability and race

BACKGROUND: Differences in self-reported disability may be found for older black and white adults with knee osteoarthritis (OA). METHODS: This secondary analysis of data from a randomized single-blind clinical trial examined race differences in the relationship between self-reports and timed performance tests of walking. Study participants were 518 older adults (131 blacks, 387 whites), including 363 women and 155 men, with an average age of 68.6 years. RESULTS: Older black and white adults with radiographically documented knee OA reported equivalent functional ability and pain severity. However, both blacks' OA severity rating and tested performance were significantly worse than those of whites. Self-report and tested walking performance were significantly less correlated among black older adults than among white older adults. Analyses of potential confounding variables documented that the difference was not due to marital status, gender, education, income, body mass index, comorbidity, pain level, OA severity or general health. CONCLUSIONS: Self-reports of OA disability were less related to tested performance for walking among black older adults. Clinicians' knowledge of black patients' underestimation of their disability has compelling potential for improving clinical treatment and enhancing diagnostic approaches to care of older adults.     

Dynamic association between parental monitoring and communication and adolescent risk involvement among African-American adolescents

PURPOSE: To examine: (1) the relationship between parental monitoring and communication and adolescent risk involvement over time, including consideration of their potential interaction; and (2) the effect of consistent versus inconsistent monitoring and communication over time on adolescent risk behaviors. METHODS: Baseline and follow-up data were collected from 1999-2003. A total of 817 African-American adolescents and their parents were recruited from 35 low-income urban communities in Baltimore, MD. Perceived parental monitoring, parent-adolescent communication and seven risk behaviors were assessed. Logistic general estimating equation (GEE) models were performed to assess the dynamic association. RESULTS: Perceived parental monitoring had protective effects on concurrent adolescent risk involvement over two-year observation. The protective effect on girls' sexual abstinence increased significantly over time. Perceived problem communication was associated with increased risk of concurrent involvement in violent behaviors, but the effect did not change over time. For girls, the probability of engaging in sex increased greatly (from 0.3 to 0.6) for those who perceived problem communication, while it remained stable (about 0.4) for those perceiving less problem communication. CONCLUSIONS: The data confirm the protective effect of perceived parental monitoring on adolescent risk involvement. It also extends previous findings by showing the importance of consistent parental monitoring and communication.     

Prediction of Human Brain Penetration of P-glycoprotein and Breast Cancer Resistance Protein Substrates Using In Vitro Transporter Studies and Animal Models

Four P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) substrates with human cerebrospinal fluid (CSF) concentrations and preclinical neuropharmacokinetics were used to assess in vitro–in vivo extrapolation of brain penetration in preclinical species and the ability to predict human brain penetration. Unbound brain (C_b,u), unbound plasma (C_p,u), and CSF compound concentrations (C_CSF) were measured in rats and nonhuman primates (NHPs), and the unbound partition coefficients (C_b,u/C_p,u and C_CSF/C_p,u) were used to assess brain penetration. The results indicated that for P-gp and BCRP dual substrates, brain penetration was severally impaired in all species. In comparison, for P-gp substrates that are weak or non-BCRP substrates, improved brain penetration was observed in NHPs and humans than in rats. Overall, NHP appears to be more predictive of human brain penetration for P-gp substrates with weak or no interaction with BCRP than rat. Although C_CSF does not quantitatively correspond to C_b,u for efflux transporter substrates, it is mostly within 3-fold higher of C_b,u in rat and NHP, suggesting that C_CSF can be used as a surrogate for C_b,u. Taken together, a holistic approach including both in vitro transporter and in vivo neuropharmacokinetics data enables a better estimation of human brain penetration of P-gp/BCRP substrates.     

The Jefferson Scale of Empathy: a nationwide study of measurement properties,underlying components,latent variable structure,and national norms in medical students

The Jefferson Scale of Empathy (JSE) is a broadly used instrument developed to measure empathy in the context of health professions education and patient care. Evidence in support of psychometrics of the JSE has been reported in health professions students and practitioners with the exception of osteopathic medical students. This study was designed to examine measurement properties, underlying components, and latent variable structure of the JSE in a nationwide sample of first-year matriculants at U.S. colleges of osteopathic medicine, and to develop a national norm table for the assessment of JSE scores. A web-based survey was administered at the beginning of the 2017–2018 academic year which included the JSE, a scale to detect “good impression” responses, and demographic/background information. Usable surveys were received from 6009 students enrolled in 41 college campuses (median response rate?=?92%). The JSE mean score and standard deviation for the sample were 116.54 and 10.85, respectively. Item-total score correlations were positive and statistically significant (p?<?0.01), and Cronbach α?=?0.82. Significant gender differences were observed on the JSE scores in favor of women. Also, significant differences were found on item scores between top and bottom third scorers on the JSE. Three factors of Perspective Taking, Compassionate Care, and Walking in Patient’s Shoes emerged in an exploratory factor analysis by using half of the sample. Results of confirmatory factor analysis with another half of the sample confirmed the 3-factor model. We also developed a national norm table which is the first to assess students’ JSE scores against national data.